Prospective drug treatment caused by the wrong twisting process of protein

The discovery by scientists at Scripps Research Institute has yielded a prospect of a new drug to treat people suffering from the wrong twisting of proteins. According to results published by pharmaceutical firm FoldRx Pharmaceuticals, Inc. On July 21, the new drug was able to prevent further progression in patients with starchy polyneuropathy caused by transthyretin coding gene mutations (TTsthyretin (TTR) amyloid polyneuropathy). (ATTR-PN)).

'I am very excited by the prospect of a drug that can help patients with starchy polyneuropathy occur due to the transthyretin coding gene mutation (ATTR-PN),' said Dr. Jeffery Kelly, co-founder. FoldRx shared. The Scripps Research Institute of Kelly has laid the groundwork for this treatment strategy and discovered the new drug mentioned above. 'Furthermore, this is the first pharmacological evidence to demonstrate the hypothesis of the research community. biochemical rescue of the causes of human degenerative starch diseases, including Alzheimer's. Taifamidis was developed over many years of basic scientific research with funding from the National Institutes of Health, the Skaggs Biochemical Institute, and the Lita Annenberg Hazen Foundation.

ATTR-PN is a rare inherited disease associated with the wrong twisting of proteins, also known as Familial Amyloid Polyneuropathy (Familial Amyloid Polyneuropathy). This is a slow, harmful, progressive disease that can cause loss of sensation, muscle weakness, and impaired autonomic neurological function (including intestinal disorders and secretory problems) urethra), and eventually lead to death . The only treatment currently available is liver transplantation.

The results of Phase II / III clinical studies of FoldRx show that when treated with oral tafamidis drugs, it will effectively prevent the progression of the disease and reduce the psychological impact after 18 months compared to placebo. The study also showed that tafamidis is safe and has no side effects.

'We are excited with the test results and hope that this breakthrough treatment will soon reach all patients in the world,' said Dr. Richard Labaudinière, President and CEO of FoldRx. said. 'We plan to discuss with US and European regulators later this year and bring this drug to market in 2010. '

False twist of protetin (photo: bio.huji.ac.il)

Continuing positive results

Starch degradation associated with transthyretin (TTR) is a disease caused by the misleading process of protein binding (after the protein binds, it is combined into starch fibers). These fibers remain in the body parts, hindering the normal function of these organs. In the case of TTR-associated polyneuropathy, a protein called transthyretin (TTR) performs wrong twisting, starch fibers will accumulate in peripheral neuron tissue to direct limbs and organs. . In the case of TTR-associated starchy myocarditis, starch fibers will get into the heart, causing heart failure. The common variant, V122I, is found in 4% of African Americans. Original TTR (normal form) can also form starch fibers, especially in the elderly body;About 15% to 25% of people over 80 years of age have recorded starch fibers present in the heart that could lead to myocarditis.

In 2001, Kelly, Dean of the Department of Molecular & Experimental Medicine with Lita Annenberg Hazen, a professor of chemistry, a member of the Skaggs Biochemistry Institute at Scripps Research Institute and colleagues, published a TTR mutant super molecule. of a suppressor when incorporated into TTR protein will prevent proteins from splitting, twisting and forming starch fibers. This explains why patients with harmful TTR mutations and 'reductant' mutations have only mild disease manifestations. (Science, 293 (5539): 2459 - 2462, September 28, 2001).

More than a year later, the group published more research results on the effectiveness of using small molecules with the aim of stabilizing the normal twisting process of TTR, preventing this protein from performing twisting. false. With this method, the researchers can prevent the formation of starch fibers by mimicking the mechanism of the TTR 'reducing agent', described in the previous study. (Science, 299 (5607): 713 - 716, January 31, 2003).

These two basic studies are supported by the NIDDK Institute of the National Institute of Health, Skaggs Biochemistry Institute, Lita Annenberg Hazen Foundation and many other agencies.